Bioterrorism has recently been elevated as a major concern as both military and civilian populations have been targeted for attack with anthrax spores through the US Postal Service. This attack has put the United States on high alert and has been a major impetus to the restructuring of our federal government to include a Department of Homeland Security. These attacks have generated the need for new methods to rapidly respond to the threat of a biological attack to not only anthrax but also to other highly infectious and deadly diseases, including influenza A virus. Vaccination is considered to be one of the best solutions for preventing infection of a biological attack. Immunizations against biological agents have a long history of protecting large populations against a variety of biological agents. However technologies that enable the rapid development and mass production of new vaccines in response to these diseases is not available. In response to this challenge, the Company has developed the VesiVax(r) system that consists of a flexible and easily modified gene cassette designed to rapidly engineer and produce antigen fusion proteins that can easily be formulated into liposomes possessing potent immunostimulating properties. VesiVax(r) vaccines offer a safer and more effective approach to vaccination because they present specific antigens to the immune system without the problems associated with whole pathogen vaccines. The primary objective of this project is to show that we can generate five matrix 2 peptides conforming to known sequences of various influenza A viruses known to cause pandemic infections. These five epitopes will represent 54% of the known influenza A virus matrix 2 proteins sequenced. Considering that all the pandemic subtypes have been H1N1, H3N2 and H2N2 (with H5N1 and H9N2 having pandemic potential), 83% of the pandemic influenza A virus subtypes would be represented in these five protein subunit vaccine antigens. These VesiVax(r) matrix 2 vaccines will be tested in mouse models and challenged with a lethal dose of a homotypic and heterotypic influenza A virus. Vaccines eliciting a protective response will be used to vaccinate mice, which have been genetically altered to remove key immunological proteins, in an attempt to elucidate the protective immune function of the vaccines.